Advanced pre-clinical evaluation of sphingosine kinase 1-targeting agents as a therapy for acute myeloid leukaemia


Professor Stuart Maxwell Pitson

University of South Australia (SA)


2024 - 2027

The Research

Leukemias are the second most frequently diagnosed cancer and among the leading causes of cancer death. Acute myeloid leukaemia (AML) is one of the most common forms of leukaemia in adults and outcomes are frequently poor, with overall survival of only 1-2 years for some subtypes. Conventional chemotherapeutics have remained the frontline AML treatment regimen for over 30 years, and despite being often highly effective at achieving initial disease remission, these responses are often short-lived resulting in patient relapse and death. Indeed, in some AML subtypes, 5-year survival rates are as low as 10%, meaning new therapies are desperately needed. Targeted therapies are continually being developed and assessed in the clinical setting and despite highly variable complete remission rates, only modest improvements in overall survival have been observed (the majority less than 12 months).

The Bcl-2 inhibitor venetoclax is one such agent that has provided promise as an AML therapy; however, responses to venetoclax are short-lived and acquired resistance has emerged as a major problem to achieve deep durable disease remission. This proposal builds on the exciting concept, supported by our extensive published evidence, that targeting the pro-survival protein, sphingosine kinase 1 (SK1) is a viable and attractive therapeutic approach for AML.


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